The transcription factor interferon regulatory factor 1 (IRF-1) is important during the maturation of natural killer 1.1+ T cell receptor-α/β+ (NK1+ T) cells, natural killer cells, and intestinal intraepithelial T cells

In contrast to conventional T cells, natural killer (NK) 1.1(+) T cell receptor (TCR)-alpha/beta(+) (NK1(+)T) cells, NK cells, and intestinal intraepithelial lymphocytes (IELs) bearing CD8-alpha/alpha chains constitutively express the interleukin (IL)-2 receptor (R)beta/15R beta chain. Recent studies have indicated that IL-2R beta/15R beta chain is required for the development of these lymphocyte subsets, outlining; the importance of IL-15. In this study, we investigated the development of these lymphocyte subsets in interferon regulatory factor I-deficient (IRF-1(-/-)) mice. Surprisingly, all of these lymphocyte subsets were severely reduced in IRF-1(-/-) mice. Within CD8-alpha/alpha(+) intestinal IEL subset, TCR-gamma/G(+) cells and TCR-alpha/beta(+) cells were equally affected by IRF gene disruption. In contrast to intestinal TCR-gamma/G(+) cells, thymic TCR-gamma/delta(+) cells developed normally in IRF-1(-/-) mice. Northern blot analysis further revealed that the induction of IL-15 messenger RNA was impaired in IRF-1(-/-) bone marrow cells, and the recovery of these lymphocyte subsets was observed when IRF-1(-/-) cells were cultured with IL-lj in vitro. These data indicate that IRF-1 regulates IL-15 gene expression, which may control the development of NK1(+)T cells, NK cells, and CD8-alpha/alpha(+) IELs.